EP2769321B1 - Verfahren zur verbesserung der diagnose einer entzündlichen darmerkrankung - Google Patents

Verfahren zur verbesserung der diagnose einer entzündlichen darmerkrankung Download PDF

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EP2769321B1
EP2769321B1 EP12841790.4A EP12841790A EP2769321B1 EP 2769321 B1 EP2769321 B1 EP 2769321B1 EP 12841790 A EP12841790 A EP 12841790A EP 2769321 B1 EP2769321 B1 EP 2769321B1
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sample
ibd
antibody
markers
disease
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EP2769321A4 (de
EP2769321A1 (de
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Fred Princen
Steven LOCKTON
Lisa J. Croner
Frederick A. Fletcher
Thomas STOCKFISCH
Sharat Singh
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Nestec SA
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Claims (14)

  1. Verfahren zum Diagnostizieren entzündlicher Darmerkrankung (IBD) und/oder eines klinischen Untertyps davon in einem Individuum, wobei das Verfahren Folgendes umfasst:
    (a) Analysieren einer von dem Individuum erhaltenen Probe, um Anwesenheit oder Niveau oder Genotyp von mindestens jedem der folgenden Marker zu bestimmen, um ein Markerprofil zu erhalten: (i) Anwesenheit oder Niveau von jedem der serologischen Marker ASCA-A, ASCA-G, ANCA, pANCA, Anti-OmpC-Antikörper, Anti-CBirl-Antikörper, Anti-FlaX-Antikörper, und Anti-A4-Fla2-Antikörper; (ii) Anwesenheit oder Niveau von jedem der Entzündungsmarker VEGF, ICAM, VCAM, SAA, und CRP; und (iii) Genotyp von jedem der genetischen Marker ATG16L1, ECMI, NKX2-3, und STAT3;
    (b) Anwenden einer ersten statistischen Stichprobenanalyse auf das Markerprofil, um eine erste Modellpunktzahl zu berechnen und die erste Modellpunktzahl mit einem ersten Grenzwert zu vergleichen, um eine Entscheidung zu erhalten, ob die Probe eine IBD-Probe oder eine Nicht-IBD-Probe ist;
    (c) wenn die Probe eine IBD-Probe ist, Anwenden eines Entscheidungsbaumes auf die IBD-Probe, um zu bestimmen, ob die IBD-Probe eine oder keine nicht eindeutige Probe ist,
    wobei die IBD-Probe eine nicht eindeutige Probe ist, wenn die IBD-Probe ein ANCA-Niveau größer als eine Quartilpunktzahl von 3 (> Q3) aufweist, pANCA2-positiv ist, und ein Niveau von Anti-CBirl-Antikörpern oder Anti-A4-Fla2-Antikörpern oder Anti-FlaX-Antikörpern > Q3 aufweist, oder
    wobei die IBD-Probe eine nicht eindeutige Probe ist, wenn die IBD-Probe pANCA2-positiv ist und zwei von drei Markern, ausgewählt aus Anti-CBirl-Antikörpern, Anti-A4-Fla2-Antikörpern, und Anti-FlaX-Antikörpern > Q3, exprimiert, und
    wobei die Anwesenheit oder das Niveau von pANCA zur der Bestimmung des Wertes von pANCA2 verwendet wird; und
    (d) wenn die IBD-Probe keine nicht eindeutige Probe ist, Anwenden einer zweiten statistischen Stichprobenanalyse auf die IBD-Probe, um eine zweite Modellpunktzahl zu berechnen und die zweite Modellpunktzahl mit einem zweiten Grenzwert zu vergleichen, um einen klinischen Untertyp von IBDi zu bestimmen,
    wobei die zweite statistische Stichprobenanalyse (i) auf der Anwesenheit oder dem Niveau von ASCA-A, ASCA-G, ANCA, pANCA, Anti-OmpC-Antikörpern, Anti-CBirl-Antikörpern, Anti-FlaX-Antikörpern, Anti-A4-Fla2-Antikörpern und VEGF in der Probe und (ii) des Genotyps von ECMI und STAT3 in der Probe basiert.
  2. Verfahren nach Anspruch 1, wobei die Anwesenheit oder das Niveau jedes der serologischen Marker oder Entzündungsmarker unabhängig voneinander durch ein Hybridisierungsassay, verstärkungsbasiertes Assay, Immunoassay, oder immunohistochemisches Assay bestimmt werden.
  3. Verfahren nach Anspruch 1, wobei der Genotyp eines jeden der genetischen Marker unabhängig voneinander durch Genotypisieren für die Anwesenheit oder Abwesenheit eines Einzel-Nucleotid-Polymorphismus (SNP) in jedem der genetischen Marker bestimmt wird.
  4. Verfahren nach Anspruch 3, wobei der SNP rs2241880 für ATG16L1, rs3737240 für ECMI, rs10883365 für NKX2-3, und/oder rs744166 für STAT3 ist.
  5. Verfahren nach Anspruch 1, wobei der klinische Untertyp von IBD Morbus Crohn (CD) oder Colitis ulcerosa (UC) ist.
  6. Verfahren nach Anspruch 1, wobei die Probe ausgewählt ist aus der Gruppe bestehend aus Serum, Plasma, Vollblut, und Stuhl.
  7. Verfahren nach Anspruch 1, wobei
    - wenn pANCA-Werte 0 oder +1 sind, der pANCA2-Wert negativ ist; oder
    - wenn pANCA-Werte +2, +3 oder +4 sind, der pANCA2-Wert positiv ist.
  8. Verfahren nach Anspruch 7, wobei in der pANCA2-negativen Probe, weiterhin umfassend:
    (a) Bestimmen, ob die pANCA2-negative Probe Morbus Crohn direkt durch Messen eines Serummarkerpanels vorhersagt, wobei das Serummarkerpanel ein Teil der Gruppe bestehend aus ASCA-IgA, ASCA-IgG, und OmpC-IgA ist und Vergleichen eines jeden der Serummarker des Serummarkerpanels mit einem Grenzwert, um zu bestimmen, ob die Probe mit Morbus Crohn konsistent ist; oder
    (b) Bestimmen, ob die pANCA2-negative Probe mit Morbus Crohn konsistent ist durch Messen eines CD-Zählpanels, wobei das CD-Zählpanel ein Teil der Gruppe bestehend aus ASCA-IgA, ASCA-IgG, OmpC-IgA, CBirl-IgG, A4-Fla2-IgG und FlaX-IgG zum Bilden eines CD-Zählwerts ist, wobei, wenn der CD-Zählwert größer als oder gleich 2 ist, die Probe mit Morbus Crohn konsistent ist; oder
    (c) Bestimmen, ob die pANCA2-negative Probe, die einen pANCA-Wert von null aufweist, mit IBD konsistent oder inkonsistent ist, durch Messen von ANCA ELISA und Vergleichen des ANCA-ELISA-Werts mit einem Referenzwert unter Berücksichtigung, dass der CD-Zählwert bestimmt, ob die Probe mit IBD konsistent oder inkonsistent ist; oder
    (d) Bestimmen, ob die pANCA2-negative Probe, die einen pANCA-Wert von null aufweist, mit IBD konsistent oder für IBD nicht eindeutig ist, durch Messen von ANCA ELISA und Vergleichen des ANCA-ELISA-Werts unter Berücksichtigung, dass der CD-Zählwert bestimmt, ob die Probe mit IBD konsistent oder inkonsistent oder mit IBD konsistent und nicht eindeutig für Morbus Crohn oder Colitis ulcerosa ist; oder
    (e) Bestimmen, ob die pANCA2-negative Probe, die einen pANCA-Wert von eins aufweist, mit IBD konsistent oder inkonsistent ist durch Messen von ANCA ELISA und Vergleichen des ANCA-ELISA-Werts mit einem Grenzwert, um zu bestimmen, ob die Probe mit IBD konsistent oder inkonsistent ist.
  9. Verfahren nach Anspruch 8, wobei in Abschnitt (a) vorstehend, wenn der Wert für
    - ASCA-IgA größer oder gleich 69 EU/mL ist; oder
    - ASCA-IgG größer oder gleich 40 EU/mL ist; oder
    - OmpC-IgA größer oder gleich 60 EU/mL ist;
    die Probe als konsistent mit Morbus Crohn bezeichnet wird.
  10. Verfahren nach Anspruch 8, wobei in Abschnitt (b) vorstehend, weiterhin umfassend das Zuweisen des CD-Zählwerts, durch Bestimmen, ob
    i. ASCA-IgA größer oder gleich 8,5 EU/mL ist, dann Addieren von +1 zu dem CD-Zählwert;
    ii. ASCA-IgG größer oder gleich 17,8 EU/mL ist, dann Addieren von +1 zu dem CD-Zählwert;
    iii. OmpC-IgA größer oder gleich 10,9 EU/mL ist, dann Addieren von +1 zu dem CD-Zählwert;
    iv. 2 oder mehr Flagellin-Marker über ihren jeweiligen Referenzbereichen liegen, Addieren von +1 zu dem CD-Zählwert;
    v. jeder Flagellin größer oder gleich 100 EU/mL ist, dann Addieren von +1 zu dem CD-Zählwert;
    und wenn der Gesamt-CD-Zählwert größer oder gleich 2 ist, dann Bezeichnen der Probe als konsistent mit Morbus Crohn.
  11. Verfahren nach Anspruch 10, wobei der Referenzwert für
    - CBirl-IgG größer oder gleich 78,4 EU/mL ist; oder
    - A4-Fla2-IgG größer oder gleich 44,8 EU/mL ist; oder
    - FlaX-IgG größer oder gleich 33,4 EU/mL ist.
  12. Verfahren nach Anspruch 8, wobei in Abschnitt (c) vorstehend, wenn pANCA null ist (nicht nachgewiesen), weiterhin umfassend:
    i. Bezeichnen der Probe als mit IBD inkonsistent, wenn ANCA ELISA geringer als 20 EU/mL ist; oder
    ii. Bezeichnen der Probe als konsistent mit Colitis ulcerosa, wenn ANCA ELISA größer als 27,4 EU/mL ist; oder
    iii. Bezeichnen der Probe als mit IBD inkonsistent, wenn ANCA ELISA größer oder gleich 20 und geringer oder gleich 27,4 EU/mL ist und der CD-Zählwert null ist; oder
    iv. Bezeichnen der Probe als mit IBD konsistent, jedoch als nicht eindeutig für Morbus Crohn oder Colitis ulcerosa, wenn ANCA ELISA größer oder gleich 20 und geringer oder gleich 27,4 EU/mL ist und der CD-Zählwert eins ist.
  13. Verfahren nach Anspruch 8, wobei, wenn pANCA eins ist, weiterhin umfassend:
    i. Bezeichnen der Probe als mit IBD inkonsistent, wenn ANCA ELISA geringer als 13,7 EU/mL ist; oder
    ii. Bezeichnen der Probe als vereinbar mit Colitis ulcerosa, wenn ANCA ELISA größer als der gleich 13,7 EU/mL ist; oder
  14. Verfahren zum Diagnostizieren entzündlicher Darmerkrankung (IBD) und/oder eines klinischen Untertyps davon in einem Individuum, wobei das Verfahren Folgendes umfasst:
    (a) Analysieren einer von dem Individuum erhaltenen Probe, um Anwesenheit oder Niveau oder Genotyp von mindestens jedem der folgenden Marker zu bestimmen, um ein Markerprofil zu erhalten: (i) Die Anwesenheit oder das Niveau von jedem der serologischen Marker ASCA-A, ASCA-G, ANCA, pANCA, Anti-OmpC-Antikörper, Anti-CBirl-Antikörper, Anti-FlaX-Antikörper, und Anti-A4-Fla2-Antikörper; (ii) Anwesenheit oder Niveau von jedem der Entzündungsmarker VEGF, ICAM, VCAM, SAA, und CRP; und (iii) des Genotyps von jedem der genetischen Marker ATG16L1, ECMI, NKX2-3, und STAT3;
    (b) Anwenden einer ersten statistischen Stichprobenanalyse auf das Markerprofil, um zu bestimmen, ob diese Probe eine IBD-Probe oder eine Nicht-IBD-Probe ist mit einer Empfindlichkeit von mindestens 70 %;
    (c) wenn die Probe eine IBD-Probe ist, Anwenden eines Entscheidungsbaumes auf die IBD-Probe, um zu bestimmen, ob die IBD-Probe eine oder keine nicht eindeutige Probe ist,
    wobei die IBD-Probe eine nicht eindeutige Probe ist, wenn die IBD-Probe ein ANCA-Niveau größer als eine Quartilpunktzahl von 3 (> Q3) aufweist, pANCA2-positiv ist, und ein Niveau von Anti-CBirl-Antikörper oder Anti-A4-Fla2-Antikörper oder Anti-FlaX-Antikörper > Q3 aufweist, oder
    wobei die IBD-Probe eine nicht eindeutige Probe ist, wenn die IBD-Probe pANCA2-positiv ist und zwei von drei Markern, ausgewählt aus Anti-CBirl-Antikörper, Anti-A4-Fla2-Antikörper, und Anti-FlaX-Antikörper > Q3, exprimiert, und
    wobei die Anwesenheit oder das Niveau von pANCA zu der Bestimmung des Wertes von pANCA2 verwendet wird; und
    (d) wenn die IBD-Probe keine nicht eindeutige Probe ist, dann Anwenden einer zweiten statistischen Stichprobenanalyse auf die IBD-Probe zum Bestimmen eines klinischen Untertyps von IBD mit einer Empfindlichkeit von mindestens 85 % für Morbus Crohn (CD) und einer Empfindlichkeit von mindestens 95 % für Colitis ulcerosa (UC),
    wobei die zweite statistische Stichprobenanalyse (i) auf der Anwesenheit oder dem Niveau von ASCA-A, ASCA-G, ANCA, pANCA, Anti-OmpC-Antikörper, Anti-CBirl-Antikörper, Anti-FlaX-Antikörper, Anti-A4-Fla2-Antikörper und VEGF in der Probe basiert und (ii) des Genotyps von ECMI und STAT3 in der Probe.
EP12841790.4A 2011-10-21 2012-10-19 Verfahren zur verbesserung der diagnose einer entzündlichen darmerkrankung Active EP2769321B1 (de)

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Families Citing this family (44)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2010062960A2 (en) 2008-11-26 2010-06-03 Cedars-Sinai Medical Center METHODS OF DETERMINING RESPONSIVENESS TO ANTI-TNFα THERAPY IN INFLAMMATORY BOWEL DISEASE
NZ595471A (en) 2009-04-14 2014-01-31 Nestec Sa Inflammatory bowel disease prognostics
WO2015067913A1 (en) 2013-11-07 2015-05-14 Diagnodus Limited Biomarkers
SG194710A1 (en) 2011-05-10 2013-12-30 Nestec Sa Methods of disease activity profiling for personalized therapy management
CN105246501B (zh) 2013-03-27 2021-01-12 雪松-西奈医学中心 通过抑制tl1a的功能和相关信号传导途径来减轻并逆转纤维化和炎症
WO2014182689A1 (en) * 2013-05-06 2014-11-13 Yacyshyn Bruce R Method of using biomarkers in predicting inflammatory bowel disease
BR112015029320A8 (pt) * 2013-05-24 2023-01-03 Nestec Sa Ensaios específicos de vias para predição de diagnóstico de síndrome do intestino irritável
EP3022295A4 (de) 2013-07-19 2017-03-01 Cedars-Sinai Medical Center Signatur des tl1a (tnfsf15)-signalweges
US11568982B1 (en) 2014-02-17 2023-01-31 Health at Scale Corporation System to improve the logistics of clinical care by selectively matching patients to providers
EP3167392A4 (de) * 2014-07-11 2018-08-01 Matatu Inc. Verwendung von darmmikrobiom als prädiktor des wachstums oder der gesundheit von tieren
CN104131102B (zh) * 2014-08-07 2016-06-15 马飞 一种判断nsclc患者对吉非替尼治疗反应性的试剂盒
US11809501B2 (en) * 2014-08-28 2023-11-07 Ebay Inc. Systems, apparatuses, and methods for providing a ranking based recommendation
WO2016088068A1 (en) * 2014-12-02 2016-06-09 Nestec S.A. Methods for establishing a vedolizumab dosing regimen to treat patients with irritable bowel disease
CN107548498A (zh) 2015-01-20 2018-01-05 南托米克斯有限责任公司 用于反应预测高级别膀胱癌中的化疗的系统和方法
CA2978708A1 (en) * 2015-03-03 2016-09-09 Nantomics, Llc Ensemble-based research recommendation systems and methods
US11037070B2 (en) * 2015-04-29 2021-06-15 Siemens Healthcare Gmbh Diagnostic test planning using machine learning techniques
US11946927B2 (en) 2016-03-14 2024-04-02 Musidora Biotechnology Llc Process and system for identifying individuals having a high risk of inflammatory bowel disease and a method of treatment
US10295527B2 (en) 2016-03-14 2019-05-21 Bruce Yacyshyn Process and system for predicting responders and non-responders to mesalamine treatment of ulcerative colitis
EP3430172A4 (de) 2016-03-17 2019-08-21 Cedars-Sinai Medical Center Verfahren zur diagnose einer entzündlichen darmerkrankung durch rnaset2
KR20230003433A (ko) * 2016-05-20 2023-01-05 세다르스-신나이 메디칼 센터 유전자에 기반한 염증성 장 질환의 진단
JP7111322B2 (ja) * 2016-12-02 2022-08-02 国立大学法人 東京大学 線維化関連分子に対する抗体およびその医療応用
EP3554362A4 (de) * 2016-12-14 2020-08-12 Warren, Tracy System und verfahren zur entwicklung und verwendung einer mikrobiombasierten aktionskomponente für die patientengesundheit
US11978543B2 (en) 2016-12-14 2024-05-07 Astarte Medical Partners Inc. System and methods for developing and using a microbiome-based action component
US10409734B1 (en) * 2017-03-27 2019-09-10 Symantec Corporation Systems and methods for controlling auxiliary device access to computing devices based on device functionality descriptors
CN108784666B (zh) * 2017-05-04 2023-01-13 深圳市生码医疗科技有限公司 连续监测心血管的精准医疗系统及数据处理方法
JP2020523560A (ja) * 2017-05-31 2020-08-06 プロメテウス バイオサイエンシーズ インコーポレイテッド クローン病患者の粘膜治癒を評価する方法
US11244454B2 (en) * 2018-04-03 2022-02-08 Boston Scientific Scimed, Inc. Systems and methods for diagnosing and/or monitoring disease
EP3818544A1 (de) * 2018-07-05 2021-05-12 Boston Scientific Scimed, Inc. Vorrichtungen, systeme und verfahren zur bestimmung von entzündungen und/oder fibrose
WO2020041287A1 (en) * 2018-08-21 2020-02-27 Yacyshyn Bruce R Process and system for identifying individuals having a high risk of inflammatory bowel disease and a method of treatment
CA3121167A1 (en) * 2018-11-29 2020-06-04 Cedars-Sinai Medical Center Methods of stratifying and treating a sub-population of inflammatory bowel disease patients
WO2020117795A1 (en) * 2018-12-04 2020-06-11 Prometheus Biosciences, Inc. Assessment and monitoring of mucosal healing in children and adults with crohn's disease
EP3935581A4 (de) 2019-03-04 2022-11-30 Iocurrents, Inc. Datenkompression und -kommunikation mit maschinenlernung
WO2020219549A1 (en) * 2019-04-23 2020-10-29 Cedars-Sinai Medical Center Methods and systems for assessing inflammatory disease with deep learning
JP2022532381A (ja) * 2019-05-16 2022-07-14 プロサイセデクス インコーポレイティド Ｖｃａｍ－１及びカルプロテクチンのための分析検出方法
CN110373457B (zh) * 2019-06-20 2023-03-14 镇江市第一人民医院 一种用于溃疡性结肠炎诊断的mRNA标志物及其应用
CN111417124A (zh) * 2019-06-28 2020-07-14 西南交通大学 在认知无线网络环境下频谱感知的方法
US11610679B1 (en) * 2020-04-20 2023-03-21 Health at Scale Corporation Prediction and prevention of medical events using machine-learning algorithms
WO2021247548A1 (en) * 2020-06-03 2021-12-09 Cedars-Sinai Medical Center Treatments for a sub-population of inflammatory bowel disease patients
WO2022061346A1 (en) * 2020-09-16 2022-03-24 Northwestern University Classification of functional lumen imaging probe data
WO2022076372A1 (en) * 2020-10-05 2022-04-14 Cedars-Sinai Medical Center Methods and systems for stratifying inflammatory bowel disease patients
US20240044916A1 (en) * 2020-12-11 2024-02-08 Icahn School Of Medicine At Mount Sinai Methods of monitoring inflammatory bowel diseases
WO2022177963A1 (en) * 2021-02-17 2022-08-25 Prometheus Biosciences, Inc. Anti-cd30l antibodies and uses thereof
WO2023047257A1 (en) * 2021-09-22 2023-03-30 Janssen Research & Development, Llc Automated estimation of ulcerative colitis severity from endoscopy videos using ordinal multi-instance learning
WO2023147139A1 (en) * 2022-01-28 2023-08-03 University Of Southern California Identifying non-disease patients using a disease related assay and analysis in the liquid biopsy

Family Cites Families (60)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4277250A (en) 1979-12-10 1981-07-07 Baylor College Of Medicine Methods for detecting and quantifying occult blood
JPH0684970B2 (ja) 1987-03-31 1994-10-26 株式会社京都医科学研究所 糞便中の潜血検出方法
US5081040A (en) 1987-06-29 1992-01-14 Helena Laboratories Corporation Composition and kit for testing for occult blood in human and animal excretions, fluids, or tissue matrixes
US6867195B1 (en) 1989-03-21 2005-03-15 Vical Incorporated Lipid-mediated polynucleotide administration to reduce likelihood of subject's becoming infected
JPH0736013B2 (ja) 1991-04-27 1995-04-19 一男 田畑 潜血検出用試薬
US5885527A (en) 1992-05-21 1999-03-23 Biosite Diagnostics, Inc. Diagnostic devices and apparatus for the controlled movement of reagents without membrances
DK0615129T3 (da) 1993-03-10 2000-08-07 Cedars Sinai Medical Center Fremgangsmåder til selektiv påvisning af perinukleært anti-neutrophilt cytoplasmatisk antistof fra ulcerativ colitis eller
US5830675A (en) 1993-03-10 1998-11-03 Cedars-Sinai Medical Center Methods for selectively detecting perinuclear anti-neutrophil cytoplasmic antibody of ulcerative colitis, primary sclerosing cholangitis, or type 1 autoimmune hepatitis
US5972901A (en) 1994-03-23 1999-10-26 Case Western Reserve University Serpin enzyme complex receptor--mediated gene transfer
US6077835A (en) 1994-03-23 2000-06-20 Case Western Reserve University Delivery of compacted nucleic acid to cells
EP0752005B1 (de) 1994-03-23 2008-10-08 Ohio University Kompaktnukleinsäure und ihre verabreichung in zellen
US5844107A (en) 1994-03-23 1998-12-01 Case Western Reserve University Compacted nucleic acids and their delivery to cells
US5916748A (en) 1996-04-12 1999-06-29 Cedars-Sinai Medical Center Method of diagnosing a clinical subtype of crohn's disease with features of ulcerative colitis
US5932429A (en) 1996-04-12 1999-08-03 Cedars-Sinai Medical Center Methods of diagnosing clinical subtypes of crohn's disease
US6074835A (en) 1996-04-12 2000-06-13 Regents Of The Univ. Of California Diagnosis, prevention and treatment of ulcerative colitis, and clinical subtypes thereof, using histone H1
US6033864A (en) 1996-04-12 2000-03-07 The Regents Of The University Of California Diagnosis, prevention and treatment of ulcerative colitis, and clinical subtypes thereof, using microbial UC pANCA antigens
US5750479A (en) 1997-02-14 1998-05-12 Bandon Corp. Enclosed fluid system conditioner and process therefor
AU4145597A (en) 1997-02-20 1998-09-09 Cedars-Sinai Medical Center Ulcerative colitis panca secretory vesicle antigen and methods of using sa me
US6218129B1 (en) 1998-05-15 2001-04-17 Prometheus Laboratories, Inc. Inflammatory bowel disease first step assay system
US6406862B1 (en) 1998-10-06 2002-06-18 The United States Of America As Represented By The Secretary Of The Army Dip-stick assay for C-reactive protein
US6309643B1 (en) 1999-04-30 2001-10-30 The Regents Of The University Of California IBD-associated microbial antigens and methods of using same
AU5161800A (en) 1999-05-24 2000-12-12 Board Of Regents, The University Of Texas System Methods and compositions for non-viral gene therapy for treatment of hyperproliferative diseases
FR2802536B1 (fr) 1999-11-23 2003-06-13 Chru Lille Oligomannosides de synthese, leur preparation et leur utilisation a la detection d'anticorps et a la prevention d'infections
FR2806739B1 (fr) 2000-03-27 2005-02-18 Fond Jean Dausset Ceph Genes impliques dans les maladies inflammatoires de l'intestin et leur utilisation
US6838250B2 (en) 2000-03-31 2005-01-04 Ortho-Clinical Diagnostics, Inc. Immunoassay for C-reactive protein
US7138237B1 (en) 2000-05-19 2006-11-21 Cedars-Sinai Medical Center Diagnosis, prevention and treatment of Crohn's disease using the OmpC antigen
US20020042388A1 (en) 2001-05-01 2002-04-11 Cooper Mark J. Lyophilizable and enhanced compacted nucleic acids
US6821739B2 (en) 2000-10-13 2004-11-23 The Regents Of The University Of California Methods of diagnosing and treating Crohn's disease using Pseudomonas antigens
WO2002032396A2 (en) 2000-10-16 2002-04-25 Massachusetts Institute Of Technology Lipid-protein-sugar particles for delivery of nucleic acids
AU2735002A (en) 2000-10-30 2002-05-15 Univ Michigan Nod2 nucleic acids and proteins
AU4341502A (en) 2000-10-30 2002-06-11 Univ Michigan Nod2 nucleic acids and proteins
US7060442B2 (en) 2000-10-30 2006-06-13 Regents Of The University Of Michigan Modulators on Nod2 signaling
US20050164929A1 (en) 2000-11-06 2005-07-28 Lupine Logic, Inc. Methods of preventing and treating inflammatory bowel disease
US7192724B2 (en) 2000-11-14 2007-03-20 Techlab, Inc. Method for differentiating irritable bowel syndrome from inflammatory bowel disease (IBD) and for monitoring persons with IBD using total endogenous lactoferrin as a marker
JP2004535388A (ja) 2001-04-30 2004-11-25 ターゲティッド ジェネティクス コーポレイション 脂質含有薬物送達複合体およびそれらの生成方法
AU2002365279B2 (en) 2001-12-17 2009-08-13 Corixa Corporation Compositions and methods for the therapy and diagnosis of inflammatory bowel disease
US20030204507A1 (en) 2002-04-25 2003-10-30 Li Jonathan Qiang Classification of rare events with high reliability
US20040053263A1 (en) 2002-08-30 2004-03-18 Abreu Maria T. Mutations in NOD2 are associated with fibrostenosing disease in patients with Crohn's disease
CA2502976C (en) 2002-10-25 2012-05-22 Techlab, Inc. Inflammatory bowel disease and irritable bowel syndrome ibd-first chek diagnostic panel
AU2003298703A1 (en) 2002-11-22 2004-06-18 Emory University Diagnostic tests and methods for diagnosing inflammatory bowel disease
US7662569B2 (en) 2003-04-11 2010-02-16 Cedars-Sinai Medical Center Methods of assessing Crohn's disease patient phenotype by I2 serologic response
EP1617214A4 (de) 2003-04-23 2008-01-23 Eisai R&D Man Co Ltd Verfahren zur erzeugung eines krankheitsprognosemodells, verfahren zur vorhersage einer krankheitsprognose unter verwendung des modells, vorrichtung zur vorhersage einer krankheitsprognose unter verwendung des modells, deren programm und aufzeichnungsmedium
US20040242972A1 (en) 2003-05-28 2004-12-02 General Electric Company Method, system and computer product for prognosis of a medical disorder
US20050060295A1 (en) 2003-09-12 2005-03-17 Sensory Networks, Inc. Statistical classification of high-speed network data through content inspection
WO2005041896A2 (en) 2003-11-03 2005-05-12 Duke University Methods of identifying individuals at risk of perioperative bleeding, renal dysfunction or stroke
CA2554836A1 (en) 2004-02-05 2005-08-25 Medtronic, Inc. Methods and apparatus for identifying patients at risk for life threatening arrhythmias
US7759079B2 (en) 2004-05-13 2010-07-20 Prometheus Laboratories Inc. Methods of diagnosing inflammatory bowel disease
US20060154276A1 (en) * 2004-05-13 2006-07-13 Prometheus Laboratories Inc. Methods of diagnosing inflammatory bowel disease
WO2006012472A1 (en) 2004-07-21 2006-02-02 Qualyst, Inc. Apparatus, kits and methods for evaluating binding interactions, for detecting and quantifying binding molecules, and for sample preparation
CA3204588A1 (en) 2004-12-08 2006-06-15 Cedars-Sinai Medical Center Methods for diagnosis and treatment of crohn's disease
US7873479B2 (en) 2005-12-01 2011-01-18 Prometheus Laboratories Inc. Methods of diagnosing inflammatory bowel disease
US20080085524A1 (en) * 2006-08-15 2008-04-10 Prometheus Laboratories Inc. Methods for diagnosing irritable bowel syndrome
US20100015156A1 (en) 2007-03-06 2010-01-21 Cedars-Sinai Medical Center Diagnosis of inflammatory bowel disease in children
US8153443B2 (en) 2007-05-10 2012-04-10 Cedars-Sinai Medical Center Characterization of the CBir1 antigenic response for diagnosis and treatment of Crohn's disease
KR20100138995A (ko) 2008-03-27 2010-12-31 제이엑스 닛코닛세키에너지주식회사 연료 전지 시스템과 그 부하 추종 운전 방법
WO2010056682A2 (en) * 2008-11-11 2010-05-20 Prometheus Laboratories Inc. Methods for prediction of inflammatory bowel disease (ibd) using serologic markers
NZ595471A (en) * 2009-04-14 2014-01-31 Nestec Sa Inflammatory bowel disease prognostics
AU2010266028B2 (en) * 2009-06-25 2015-04-30 Société des Produits Nestlé S.A. Methods for diagnosing irritable bowel syndrome
CA2781654A1 (en) * 2009-11-25 2011-06-03 Hua Gong Novel genomic biomarkers for irritable bowel syndrome diagnosis
CA2801575A1 (en) 2010-06-04 2011-12-08 Prometheus Laboratories Inc. Methods for improving inflammatory bowel disease diagnosis

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